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The putative flavin carrier family FlcA-C is important for Aspergillus fumigatus virulence

Patrícia A de Castro1, Jéssica Chiaratto1, Enyara Rezende Morais1

  • 1a Faculdade de Ciências Farmacêuticas de Ribeirão Preto and Faculdade de Medicina de Ribeirão Preto , Universidade de São Paulo , Ribeirão Preto , Brazil.

Virulence
|September 23, 2016
PubMed

Insights

Aspergillus fumigatus requires calcium signaling for infection. Deleting the flcA gene disrupts this, causing defects and reducing virulence in mice.

Area of Science:

  • Mycology
  • Molecular Biology
  • Pathogenesis

Background:

  • Aspergillus fumigatus is a major cause of pulmonary fungal infections.
  • Calcium signaling is crucial for A. fumigatus pathogenicity, regulated by the transcription factor CrzA.

Purpose of the Study:

  • To identify A. fumigatus genes regulated by CrzA under calcium stress.
  • To investigate the role of the putative flavin transporter, flcA, in fungal pathogenicity.

Main Methods:

  • Chromatin Immunoprecipitation followed by DNA sequencing (ChIP-seq) to identify CrzA targets.
  • Construction and phenotypic analysis of a ΔflcA null mutant.
  • Assessment of virulence in a murine infection model.

Main Results:

  • The flcA gene was identified as a CrzA target involved in calcium stress response.
  • ΔflcA mutants exhibited morphological defects and increased sensitivity to various damaging agents.
  • Calcium supplementation rescued ΔflcA growth and conidiation, indicating calcium insufficiency.
  • ΔflcA-C mutants showed reduced flavin adenine dinucleotide (FAD) levels and were avirulent.

Conclusions:

  • The flavin transporter FlcA plays a significant role in calcium homeostasis and iron metabolism in A. fumigatus.
  • FlcA is essential for A. fumigatus virulence, potentially through its involvement in flavin metabolism.
Keywords:
Aspergillus fumigatusCrzAFAD metabolismcalciumputative flavin flcA-C transporter family

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